scholarly journals Identifying Prognostic Factors for Well-Differentiated Metastatic Pancreatic Neuroendocrine Tumours: A Retrospective International Multicentre Cohort Study

2018 ◽  
Vol 107 (4) ◽  
pp. 315-323 ◽  
Author(s):  
Paula Jiménez-Fonseca ◽  
Sebastian Krug ◽  
Gianluca Tamagno ◽  
Felipe Fierro Maya ◽  
Antonio Monléon Getino ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Neuroendocrine Tumours ◽  
Curative Surgery ◽  
Risk Of Death ◽  
Pancreatic Neuroendocrine Tumours ◽  
Synchronous Metastases ◽  
Well Differentiated ◽  
The Impact

Pancreatic neuroendocrine tumours (pNETs) represent rare neoplasms of all NETs often presenting without functional activity. Many sporadic non-functioning pNET patients are already metastatic at the time of diagnosis, and the therapeutic approach to such patients is mostly palliative. In this international, multicentre, retrospective cohort study, we assessed the prognostic value of a set of anthropometric, clinical, biochemical, radiological and pathological parameters at baseline and the impact of the therapeutic strategies on the survival of patients with sporadic grade 1/2, stage IV, non-functioning pNETs. Three hundred and twelve consecutive patients diagnosed between 1993 and 2010 were included. The median overall survival (OS) was 6.6 years and survival at 5 and 10 years was 62 and 34% respectively. On univariate analysis, Eastern Cooperative Oncology Group (ECOG) status ≥2, grade 2, bilobar hepatic metastases, synchronous metastases, and high chromogranin A, alkaline-phosphatase and lactic-dehydrogenase were associated with a significant reduction of OS. Palliative/curative surgery and loco-regional hepatic interventions were significant factors improving OS. On multivariate analysis, ECOG status ≥2, synchronous metastases, Ki-67 ≥10%, and high alkaline-phosphatase correlated significantly with an increased risk of death. Both palliative/curative surgery and loco-regional hepatic interventions had a positive impact on OS. Although most parameters did not prove to be independent OS predictors at multivariate analysis, they showed a tendency towards that. Future prospective studies including larger patient populations may give greater clarity. We believe the integration of these parameters has the potential to provide a reliable prognostic score for the stratification of patients with sporadic well-differentiated metastatic non-functioning pNETs.

scholarly journals The Value of Alkaline Phosphatase-to-Albumin Ratio in Detecting Synchronous Metastases and Predicting Postoperative Relapses among Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Wentao Zhou ◽  
Yuan Fang ◽  
Xu Han ◽  
Tiantao Kuang ◽  
Xuefeng Xu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Distant Metastasis ◽  
Vascular Invasion ◽  
Biological Behavior ◽  
Neuroendocrine Neoplasm ◽  
Albumin Ratio ◽  
Pancreatic Neuroendocrine Neoplasm ◽  
Synchronous Metastases ◽  
Well Differentiated ◽  
Synchronous Distant Metastasis

Backgrounds. Pancreatic neuroendocrine neoplasm (pNEN) is a highly heterogeneous entity, presenting widely varied biological behavior as well as long-term prognosis. Reliable biomarkers are urgently needed to make risk stratifications for pNEN patients, which could be beneficial to the development of individualized therapeutic strategy in the clinical practice. Here, we aimed to evaluate the predictive and prognostic roles of serum alkaline phosphatase-to-albumin ratio (APAR) in well-differentiated pNEN patients. Methods. We retrospectively analyzed the pathologically confirmed grade 1/2 pNEN patients, who were originally treated in our hospital from February 2008 to April 2018. Univariate and multivariate analyses were performed to assess the value of APAR in detecting synchronous metastases and predicting relapses following curative resections. Results. A total of 170 eligible cases were included into analysis. Logistic univariate analysis indicated APAR (P=0.002) was significantly associated with synchronous distant metastasis among well-differentiated pNEN patients, which was further demonstrated to be an independent risk factor by multivariate analysis (odds ratio 8.127, 95% confidence interval (CI) 2.105–31.372, P=0.002). For the prognostic value, APAR (P=0.007) was statistically associated with recurrence-free survival (RFS) in nonmetastatic resected pNEN patients, but it was not an independent predictor. Further subgroup analysis showed that APAR was independently related to RFS in patients with no nerve (hazard ratio (HR) 7.685, 95% CI 1.433–41.209, P=0.017) or vascular invasion (HR 4.789, 95% CI 1.241–18.473, P=0.023), respectively. Conclusion. APAR may work as a convenient pretreatment marker to detect synchronous distant metastasis for well-differentiated pNEN patients and predict recurrences for curatively resected cases without nerve or vascular invasion. However, these findings should be further verified in prospectively well-designed studies.

CD3+ tumor-infiltrating lymphocytes (TILs) as prognostic in patients (pts) with stage II colon cancer (CC) not treated with adjuvant chemotherapy (ADJ).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 167-167
Author(s):  
Edoardo Francini ◽  
Fang-Shu Ou ◽  
Stefano Lazzi ◽  
Roberto Petrioli ◽  
Andrea Giovanni Multari ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Multivariable Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Clinical Decision ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Cox Models ◽  
Risk Of Death ◽  
The Impact

167 Background: Previous studies have reported high TILs are a favorable prognostic factor in stage II CC. However, whether the impact of TILs on overall survival (OS) differs among pts who did or did not receive ADJ is still to be determined. We assessed the prognostic value of CD3+ TILs in pts with stage II CC according to whether they received ADJ or not (no-ADJ). Methods: Pts treated with curative surgery for stage II CC (2002-2013) were identified through the Santa Maria alle Scotte Hospital database. CD3+ TILs at the invasive front, center of tumor, and stroma, were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as > 20%. Pts were classified as high or low TILs (L-TILs) and ADJ or no-ADJ. Cox models were used to assess OS with hazard ratio estimates (95% CI). Results: Of the 678 pts included (356 deaths), 137 (20%) received ADJ while 541 (80%) did not. ADJ comprised fluoropyrimidine +/- oxaliplatin. Median follow-up was 8.5 years. The distributions of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ pts had a significantly longer OS (P < .0001) regardless of the TILS rate while L-TILs/no ADJ had significantly shorter OS and higher risk of death (HR = 1.41; 95% CI, 1.06-1.88; P < .0001) [See table]. On multivariable analysis, adjusting for perforation, obstruction, T-stage, grade, < 12 lymph nodes resected, lymphovascular and perineural invasion, the adverse prognostic impact of L-TILs (vs H-TILs) in no-ADJ pts was confirmed (HR = 1.36; 95% CI 1.02, 1.82; P = .0373). Conclusions: Low CD3+ TILs rate was independently associated with shorter OS in stage II CC pts who did not receive ADJ, but was not prognostic among pts who had ADJ. These data suggest a potentially different impact of TILs in chemo-treated vs -untreated stage II CC which could affect clinical decision making. [Table: see text]

scholarly journals Association between the Use of Backpack and Static Foot Posture in Schoolchildren with Static Pronated Foot Posture: A 36-Month Cohort Study

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 800
Author(s):  
Pilar Alfageme-García ◽  
Julián Fernando Calderón-García ◽  
Alfonso Martínez-Nova ◽  
Sonia Hidalgo-Ruiz ◽  
Belinda Basilio-Fernández ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Prospective Study ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Foot Posture ◽  
The Mean ◽  
The Impact

Background: Schoolchildren often spend a lot of time carrying a backpack with school equipment, which can be very heavy. The impact a backpack may have on the pronated feet of schoolchildren is unknown. Aims: The objective of this study was to evaluate the association of the backpack use on static foot posture in schoolchildren with a pronated foot posture over 36 months of follow-up. Methods: This observational longitudinal prospective study was based on a cohort of consecutive healthy schoolchildren with pronated feet from fifteen different schools in Plasencia (Spain). The following parameters were collected and measured in all children included in the study: sex, age, height, weight, body mass index, metatarsal formula, foot shape, type of shoes, and type of schoolbag (non-backpack and backpack). Static foot posture was determined by the mean of the foot posture index (FPI). The FPI was assessed again after 36 months. Results: A total of 112 participants used a backpack when going to school. Over the 36-month follow-up period, 76 schoolchildren who had a static pronated foot posture evolve a neutral foot posture. Univariate analysis showed that the schoolchildren using backpacks were at a greater risk of not developing neutral foot (odds ratio [OR]: 2.09; 95% CI: 1.08–4.09). The multivariate analysis provided similar results, where the schoolchildren using a backpack (adjusted OR [aOR]: 1.94; 95% CI: 1.02–3.82) had a significantly greater risk of not developing a neutral foot posture. Conclusions: A weak relationship was found between backpack use and schoolchildren aged from five to eleven years with static pronated feet not developing a neutral foot posture over a follow-up period of 36 months.

scholarly journals Sociodemographic Profile and Outcomes of Patients with Non-Diffuse Large B-Cell Lymphoma (non-DLBCL) Treated at Minority-Predominant Facilities in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4868-4868
Author(s):  
Vivek Kumar ◽  
Taimur Sher ◽  
Vivek Roy ◽  
Prakash Vishnu ◽  
Anne M Hazen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell Lymphoma ◽  
The United States ◽  
Racial Minorities ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Race Ethnicity ◽  
Facility Level ◽  
The Impact

Abstract Background: Racial disparities in outcomes of cancer patients have been reported. Access to comprehensive cancer centers is associated with improved overall survival (OS) but racial/ethnic minorities may have a disparate access to such care. While the impact of treatment facility volume on outcomes has been evaluated, outcomes of centers with minority-predominant patient population have not been studied. We compared demographic profiles, facility level data and OS of patients treated at minority-predominant facilities to facilities that treated predominantly non-Hispanic Whites (NHW) with non-DLBCL. Methods: The National Cancer Database (NCDB) was used to identify all non-DLBCL patients diagnosed between 2004 and 2015. "Minority-treating facilities" were defined as facilities in the top decile by proportion for initial treatment of non-Hispanic African-Americans (NHAA), Hispanics and other races. We performed univariate and multivariate analyses to compare sociodemographic and clinical factors influencing outcomes between minority treating and non-minority treating facilities. A subgroup analysis stratified by race/ethnicity was also conducted to study the effect of treating facilities on the outcome of NHWs and minorities separately. Results: Of 1339 total facilities, 123 (9.1%) qualified as minority treating. Of 207,239 eligible patients in NCDB, 18,719 (9.03%) received treatment at the minority-treating facilities and of these, 11,190 (~60%) belonged to the minority races. Overall, 4.5% (6,988/156,664) NHWs and 30% (11,190/37,639) minorities received treatment at the minority-treating facilities. Several demographic and facility level characteristics were significantly different among the patients treated at minority-treating facilities as compared to non-minority treating facilities. Overall, significantly higher number of patients in minority-treating hospitals had lower income and education, had Medicaid coverage or lack of insurance. The OS of patients in minority treating facilities was significantly worse as compared to non-minority facilities (Figures). On multivariate analysis, patients who received treatment at minority-treating facilities were at 10% (HR=1.10, 95% CI: 1.06-1.14 p<0.001) higher risk of mortality as compared to those treated at the non-minority treating facilities. On multivariate analysis, NHAA (30% increased risk) and 'other races' (9% increased risk) were at significantly higher risk of mortality as compared to the NHW (Table 2). To study the effect of treatment at minority-treating facilities on OS among the patients of same race/ethnicity group, a multivariate analysis was also run separately for NHW and racial minorities. The NHWs who received treatment at minority-treating facilities were at 13% higher risk of death (HR=1.13, 95% CI: 1.08-1.19 p<0.001) as compared to NHWs who were treated at non-minority treating facilities. Similarly, the racial minorities who received treatment at minority treating facilities were at 8% higher risk of death (HR=1.08, 95% CI: 1.03-1.19 p=0.003) as compared to those who received treatment at the nonminority treating facilities. Conclusions:Outcomes of patients who received treatment at minority treating facilities was significantly worse than those at non-minority treating facilities. This was true for NHWs and racial minorities separately as well. Several demographic and facility level characteristics were significantly different in the two groups however OS remained worse after adjusting for them. Causes of poor outcomes at minority-treating facilities must be analyzed to mitigate them and improve outcomes for all. Figure. Figure. Disclosures Ailawadhi: Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Research Funding.

scholarly journals CUX1—Transcriptional Master Regulator of Tumor Progression in Pancreatic Neuroendocrine Tumors

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1957
Author(s):  
Sebastian Krug ◽  
Julia Weissbach ◽  
Annika Blank ◽  
Aurel Perren ◽  
Johannes Haybaeck ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Model ◽  
Neuroendocrine Tumours ◽  
Tumour Progression ◽  
Free Survival ◽  
Treatment Naïve ◽  
Pancreatic Neuroendocrine Tumours ◽  
The Impact

Recently, we identified the homeodomain transcription factor Cut homeobox 1 (CUX1) as mediator of tumour de-differentiation and metastatic behaviour in human insulinoma patients. In insulinomas, CUX1 enhanced tumour progression by stimulating proliferation and angiogenesis in vitro and in vivo. In patients with non-functional pancreatic neuroendocrine tumours (PanNET), however, the impact of CUX1 remains to be elucidated. Here, we analysed CUX1 expression in two large independent cohorts (n = 43 and n = 141 tissues) of non-functional treatment-naïve and pre-treated PanNET patients, as well as in the RIP1Tag2 mouse model of pancreatic neuroendocrine tumours. To further assess the functional role of CUX1, expression profiling of DNA damage-, proliferation- and apoptosis-associated genes was performed in CUX1-overexpressing Bon-1 cells. Validation of differentially regulated genes was performed in Bon-1 and QGP1 cells with knock-down and overexpression strategies. CUX1 expression assessed by a predefined immunoreactivity score (IRS) was significantly associated with shorter progression-free survival (PFS) of pre-treated PanNET patients (23 vs. 8 months; p = 0.005). In treatment-naïve patients, CUX1 was negatively correlated with grading and recurrence-free survival (mRFS of 39 versus 8 months; p = 0.022). In both groups, high CUX1 levels indicated a metastatic phenotype. Functionally, CUX1 upregulated expression of caspases and death associated protein kinase 1 (DAPK1), known as mediators of tumour progression and resistance to cytotoxic drugs. This was also confirmed in both cell lines and human tissues. In the RIP1Tag2 mouse model, CUX1 expression was associated with advanced tumour stage and resistance to apoptosis. In summary, we identified the transcription factor CUX1 as mediator of tumour progression in non-functional PanNET in vitro and in vivo, indicating that the CUX1-dependent signalling network is a promising target for future therapeutic intervention.

The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study

2019 ◽  
Vol 33 (6) ◽  
Author(s):  
Alfred Adiamah ◽  
Lu Ban ◽  
Joe West ◽  
David J Humes
Keyword(s):  
Gastric Cancer ◽  
Cohort Study ◽  
Venous Thromboembolism ◽  
Adjuvant Chemotherapy ◽  
Cumulative Incidence ◽  
Population Based ◽  
Risk Of Death ◽  
Increased Risk ◽  
Esophagogastric Cancer ◽  
The Impact

SUMMARY To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32–219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44–267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49–15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.

scholarly journals The Impact of Preoperative Endoscopic Ultrasound on the Surgical Management of Pancreatic Neuroendocrine Tumours

2008 ◽  
Vol 22 (10) ◽  
pp. 817-820 ◽  
Author(s):  
Fahad Alsohaibani ◽  
David Bigam ◽  
Norman Kneteman ◽  
AM James Shapiro ◽  
Gurpal Singh Sandha
Keyword(s):  
Surgical Management ◽  
Endoscopic Ultrasound ◽  
Neuroendocrine Tumours ◽  
Preoperative Assessment ◽  
Needle Aspiration ◽  
Ct Scanner ◽  
Extent Of Surgery ◽  
Pancreatic Neuroendocrine Tumours ◽  
Needle Aspiration Cytology ◽  
The Impact

BACKGROUND: Endoscopic ultrasound (EUS) is accurate in diagnosing pancreatic neuroendocrine tumours (PNETs), but its impact on surgical management is unclear.OBJECTIVE: To determine whether preoperative EUS findings altered the decision for, and extent of, surgery in patients with PNETs.METHODS: A retrospective review of patients referred for EUS because of suspected PNETs was conducted. The diagnosis of PNETs was confirmed by EUS-guided fine needle aspiration cytology, where indicated, or by surgical histology. EUS findings were compared with computed tomography (CT) findings to determine whether there was an impact on the decision for surgical management.RESULTS: Fourteen patients (10 women), with a mean age of 44 years, underwent EUS for suspected PNETs. PNETs were seen with CT in 10 of 13 patients (77%) and with EUS in 14 of 14 patients (100%). One obese patient could not fit into the CT scanner. This patient had five PNETs on EUS. Three patients with a normal CT scan were determined to have one or two PNETs on EUS. Three patients with one or two PNETs on CT were found to have five to eight PNETs on EUS. EUS altered the decision for possible surgical management in five of 14 patients (36%), either by identifying a PNET or by finding multiple and multifocal PNETs that were not visualized on CT scans.CONCLUSION: EUS is useful in the preoperative assessment of PNETs by providing information that significantly influences the decision for surgical intervention or changes the extent of the planned surgery.

scholarly journals The Impact of 68Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel J. Cuthbertson ◽  
Jorge Barriuso ◽  
Angela Lamarca ◽  
Prakash Manoharan ◽  
Thomas Westwood ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Neuroendocrine Tumours ◽  
Locally Advanced ◽  
Ct Imaging ◽  
Imaging Findings ◽  
Imaging Data ◽  
Cross Sectional ◽  
Pet Ct ◽  
Pancreatic Neuroendocrine Tumours ◽  
The Impact

ObjectivePancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of 68Gallium (68Ga)-DOTA PET/CT in managing patients with panNETs.DesignA retrospective study conducted across three tertiary UK NET referral centres.MethodsDemographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a 68Ga-DOTA PET/CT scan for a suspected panNET.ResultsWe collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 68Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, 68Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases.Conclusion68Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.

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